Prox1 is differentially localized during lens development

Abstract

Prox1, the vertebrate cognate of Drosophila Prospero, is a homeodomain protein essential for the development of the lens, liver and lymphatic system. While it is well established that the subcellular distribution of Prospero changes during development, this had not been demonstrated for Prox1. Here, high-resolution confocal microscopy demonstrated that Prox1 protein is predominately cytoplasmic in the lens placode as well as the lens epithelium and germinative zone throughout development. However during fiber cell differentiation, Prox1 protein redistributes to cell nuclei. Finally, as lens fiber cells condense their chromatin in response to lens denucleation, Prox1 remains in the nucleus but does not appear to interact with DNA. Thus, it appears that the function of Prox1, like that of its Drosophila cognate Prospero, is at least partially controlled by changes in its subcellular distribution during development.

Mafs, Prox1, and Pax6 Can Regulate Chicken βB1-Crystallin Gene Expression

“…Furthermore, this Prox1-mediated transactivation is inhibited by Pax6. Thus, the promoter activity depends on occupancy of these transcription factors on the promoter: if Pax6 concentrations are high (as seen in the lens epithelium) (19), ␤B1-crystallin gene expression is off; if Prox1 and Maf concentrations are high and Pax6 concentrations are low (as in lens fiber cells) (8,14,15), Pax6 is displaced from the promoter by c-Maf and Prox1, which stimulate ␤B1-crystallin gene expression (Fig. 8).…”

“…Pax6 cooperates with Mafs to activate crystallin genes expressed in all lens cells, such as mouse ␣A and chicken ␦1-crystallins, whereas Pax6 inhibits the expression of fiber cell preferred ␤B1 (25) and ␥-crystallins (35). Furthermore, Prox1 (14,15) and c-Maf (9) levels are strongly up-regulated in the transitional zone where fiber cells begin to form. Pax6 levels decrease sharply in chicken lens fiber cell nuclei late in embryonic development (25), coincident with the down-regulation of ␦1-crystallin and up-regulation of ␤B1-crystallin expression (60), consistent with our hypothesis.…”

“…Prox1, a divergent homeodomain protein, is expressed initially in the early lens placode and is up-regulated during fiber cell differentiation (13)(14)(15). Prox1 null lenses do not undergo lens fiber cell elongation, although the expression of several fiber cell-specific genes can be detected by RT-PCR (14).…”

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

“…Prox1 (Duncan et al, 2002) and cMaf (Kawauchi et al, 1999) show essentially overlapping expression patterns with GAD starting from the lens pit stage throughout lens development being found predominantly in the elongating lens fiber cells. Prox1 is a vertebrate homeobox gene related to the Drosophila prospero (Oliver et al, 1993;Tomarev et al, 1998), which shares domains of expression with GADs in the forebrain of mid-gestation mouse embryos (Katarova et al, 2000;Lavado and Oliver, 2007).…”

“…GAD65, EGAD, and GABA were initially detected in the lens placode, which is the site of expression of multiple transcription factors known as regulators of lens induction and fiber cell differentiation, such as Pax6, Six3, Eya, Dach1, Mafs, Sox2, Sox3, and Prox1 (Kawauchi et al, 1999;Kim et al, 1999;Wigle et al, 1999;Ogino and Yasuda, 2000;Ring et al, 2000;Duncan et al, 2002Duncan et al, , 2004Cui et al, 2004;Purcell et al, 2005). Pax6, Sox, c-Maf, and Prox1 have consensus binding sites in conserved regions of GAD65 and GAD67 genes (F. Erdélyi and Z.D.…”